Project Abstract Ambulatory adverse drug events (ADEs) continue to prompt over 4 million people to seek medical care and result in $8 billion in health care expenditures annually, despite implementation of health information technology. (health IT). One type of medication error and source of ADEs in the outpatient setting yet to be aggressively targeted is the dispensing of discontinued medications. CancelRx is an e-prescribing functionality able to communicate medication discontinuation orders between the EHR and pharmacy management software. Despite the recommendation by the National Council for Prescription Drug Programs (NCPDP) SCRIPT guidelines for more than a decade and inclusion as EHR certification criteria required to meet the Centers for Medicare and Medicaid Services' Stage 3 Meaningful use objectives, CancelRx remains widely underutilized due to unknown but perceived costs and workflow concerns. Our central hypothesis is that, by prompting removal of discontinued medications from the pharmacy management software, CancelRx will reduce medication discrepancies, prevent discontinued medications from being dispensed, and reduce ADEs. This project's specific aims are 1) to measure the impact of CancelRx on medication discrepancies in the pharmacy management software and 2) to describe the impact of CancelRx implementation on outpatient clinic and community pharmacy work systems. The mixed methods study will capitalize on the natural experiment of CancelRx implementation at UW Health, a large academic healthcare system serving over 600,000 patients in the in the Upper Midwest, with 80 outpatient clinics and 15 community pharmacies. A pre/post interrupted time series design will be utilized to determine if medications electronically discontinued in the EHR are removed from the pharmacy management software (Aim 1). Observations and interviews will be utilized to understand the intervention's impact on the clinic and pharmacy work systems (Aim 2). The rationale for the proposed research is that once the impact of CancelRx implementation on medication safety outcomes and work systems are identified, further studies focusing on how to effectively facilitate widespread dissemination and implementation in multiple settings may begin. This study is significant and innovative. It leverages a highly experienced and multidisciplinary team with expertise in pharmacy, medicine, health information services, and human factors engineering. The study will use a sociotechnical approach that is context specific and recognizes that implementation takes place in and affects existing social and technical systems. The research team is collaborating with major e-prescribing stakeholders, NCPDP and SureScripts. This approach addresses AHRQ's special interests in FOA PA-14-001 to pilot self- contained health IT projects to evaluate health IT applications that will promote effective communication and coordination of care, and make care safer by reducing harm caused in the delivery of care.